1. Cognitive Therapy in the Treatment and Prevention of Depression Steven D. Hollon, Ph.D. Vanderbilt University

2. Cognitive Pharmacotherapy Project Research Team Penn Vanderbilt Robert J. DeRubeis, Ph.D.Steven D. Hollon, Ph.D. Jay D. Amsterdam, M.D.Richard C. Shelton, M.D. Paula R. Young, Ph.D.Margaret L. Lovett, M.Ed. John P. O’Reardon, M.D.Ronald M. Salomon, M.D. Madeline M. Gladis, Ph.D.Kirsten L. Haman, Ph.D. Cory P. Newman, Ph.D.Karl N. Jannasch, Ph.D. Frances Shusman, Ph.D. Sandra Seidel, M.S.N. Brent B. Freeman, B.A.Richard C. Carson, Ph.D. Nathaniel R. Herr, B.A.Nana A. Landenberger, Ph.D. Robert Gallop, Ph.D.Laurel L. Brown, Ph.D. Aaron T. Beck, M.D. Jan Fawcett, M.D.

3. Support for this research provided by: National Institute of Mental Health GlaxoSmithKline

4. From the American Psychiatric Association’s (2000) Practice Guidelines for Major Depressive Disorder in Adults: “Antidepressant medications should be provided for moderate to severe depressive disorders unless ECT is planned.” “For example, although some data suggest that cognitive behavioral therapy alone may be effective for patients with moderate to severe major depressive disorder, most such patients will require medication.” “Antidepressant medications should be provided for moderate to severe depressive disorders unless ECT is planned.” “For example, although some data suggest that cognitive behavioral therapy alone may be effective for patients with moderate to severe major depressive disorder, most such patients will require medication.”

7. Post-treatment HRSD Scores for Severely Depressed Patients (Intake HRSD > 20) (From DeRubeis et al., 1999, Am J of Psychiatry)

8. CPT II Acute Phase (16 weeks)Continuation Phase (12 months) Follow-up Phase (12 months) CT ADM PLACEBO Prior CT (N=34) ADM (N=34) PLACEBO (N=34) (N= 60) (N= 120) (N= 60) 3 booster sessions

9. Major Entry Criteria Principal Diagnosis of Major Depressive Disorder Two consecutive (at least one week apart) scores of 20 or more on a modified 17-item Hamilton Rating Scale for Depression No Psychosis or Bipolar Disorder No Borderline, Antisocial, or Schizotypal PD No marked Substance Abuse or Dependence in previous 6 months Principal Diagnosis of Major Depressive Disorder Two consecutive (at least one week apart) scores of 20 or more on a modified 17-item Hamilton Rating Scale for Depression No Psychosis or Bipolar Disorder No Borderline, Antisocial, or Schizotypal PD No marked Substance Abuse or Dependence in previous 6 months

10. Reasons Interested Patients Were Screened Out of the Trial

11. Characteristics of the Sample

12. Demographic Information

13. Depressive Subtype and History Information

14. Comorbidity I

15. Comorbidity II

16. Acute Phase CT (N= 60) ADM (N= 120) PLACEBO (N= 60) 0246810121416 Weeks (Triple blind) Un-blinding for pill patients RandomizationRandomization (Single blind) Augmented (41%) Not Augmented (59%)

17. Dropouts in First 8 Weeks

18. Degrees of Response at 8 Weeks

19. Mean HRSD Scores Over 8 Weeks

20. Change in Depressive Symptoms from Intake to Week 8 (HRSD)

21. Dropouts in ADM and CT over 16 Weeks

22. Percent Responders (HRSD < 12) among All Assigned, Across Sites

23. Degrees of Response after 16 Weeks

24. Percent Response (HRSD < 12) by Site (16 Weeks)

25. Mean HRSD Scores Over 16 Weeks, by Site

27. Relative HRSD Change (Slopes) of ADM vs. CT from Intake to Week 16, by Site

28. Sample Characteristics on Potential Predictors of Response DemographicsHistory/Subtype Age 40+12Ever Hospitalized19% Female 59%Chronic50% Minority 18%Recurrent75% Married 33%Melancholic31% Employed 82%Atypical15% Axis I Comorbidity (73%)Axis II Comorbidity (47%) PTSD17% Cluster A 3% GAD13%Cluster B 4% Panic Dis.13%Avoidant18% Eating Dis.17%OCPD15% Subs. Use36%PD NOS16% Predicts response across ADM and CT (Prognostic) Predicts differential response to ADM vs. CT (Prescriptive)

29. Chronicity Predicts Poor Response (Prognostic)

30. Being Unemployed Predicts Poor Response (Prognostic)

31. Cluster A Predicts Poor Response (Prognostic)

32. PTSD Predicts Poor Response (Prognostic)

33. GAD Predicts Differential Response (Prescriptive)

34. CPT II Acute Phase (16 weeks)Continuation Phase (12 months) Follow-up Phase (12 months) CT ADM PLACEBO Prior CT (N=34) ADM (N=34) PLACEBO (N=34) (N= 60) (N= 120) (N= 60) 3 booster sessions

35. Intake Characteristics of Patients Who Graduated into the Continuation Phase

36. Demographic Characteristics of Patients Who Graduated into the Continuation Phase * * p <.05

37. Depressive Subtype and History Information: Patients Who Graduated into the Continuation Phase vs. Those Who Did Not * * p <.05

38. Comorbidity I: Patients Who Graduated into the Continuation Phase vs. Those Who Did Not * * p <.05

39. Comorbidity II: Patients Who Graduated into the Continuation Phase vs. Those Who Did Not * * p <.05

40. 75% 60% 19%

41. Relative Risk of Relapse During Continuation

42. Sample Characteristics on Potential Predictors of Relapse DemographicsHistory/Subtype Age: 40+12Early Onset:49% Female: 58%Dysthymic:34% Minority: 13%Recurrent:75% Married: 37%Melancholic:34% Employed: 89%Atypical:24% Axis I Comorbidity (69%)Axis II Comorbidity (49%) PTSD:10% Cluster A: 1% GAD:11%Cluster B: 1% Panic Dis.12%Avoidant:18% Eating Dis.18%OCPD:13% Subs. Use31%PD NOS:19% Predicts risk for relapse

49. Attributional Styles as a Function of Treatment Condition (CPT II) * * * *

50. ASQ and Relapse as a Function of Treatment Condition R 2 =.18 R 2 =.05

51. Sustained Improvement for All Assigned to Treatment

52. Cumulative Direct Costs of ADM and CT

53. Sustained Improvement Rates by Site

54. Treatment Response as a Function of Site and Gender

55. Response to CT as a Function of PTSD by Site

56. Therapist Competence as a Function of Experience in the Trial (Vandy)

57. Response to Treatment as a Function of Time in Trial

58. Weekly Paxil Dosage By Site

59. Weekly Paroxetine Dosage by Site and Augmentation

60. Response to Treatment as a Function of Ordinal Rank within Group (Vandy)

61. Response to Treatment as a Function of Ordinal Rank within Group (Penn)

63. ‘Normalcy’ Symptoms Syndrome Treatment phases progression to disorder RelapseRelapse RecurrenceRecurrenceRemissionRemissionRecoveryRecovery Acute Continuation Maintenance X Incomplete recovery Chronicity Response, Remission, Recovery, Relapse, Recurrence & Chronicity adapted from Kupfer & Frank 2001 ResponseResponse Time Severity RX 16 wks 12 mo

65. 25% ITT

66. Continuation Followup

67. ADM and CT (N=225) ADM (N=225) ADM (N=90+) No ADM (N=90+) 1 st R a nd o m i z a t i o n Acute Treatment (3-12 months) Continuation (6-18 months) Maintenance/Follow-up (36 months) CPT III No ADM (N=90+) ADM (N=90+) 2nd Randomization2nd Randomization RemissionRecovery Response Relapse Recurrence (twice weekly/weekly) (monthly) (weekly/biweekly) (monthly) (monthly/ quarterly) (monthly/ quarterly)

68. Medication Sequence SNRIMAOITCA SNRI or SSRI Augment

69. Using Longitudinal Data to Disentangle Cause from Consequence

80. Post-treatment HRSD Scores for Severely Depressed Patients (Intake HRSD > 20) (From DeRubeis et al., 1999, Am J of Psychiatry)

81. Attributional Styles as a Function of Treatment Condition (CPT II) * * * *

82. ASQ and Relapse as a Function of Treatment Condition R 2 =.18 R 2 =.05